Nanoemulsions

ABSTRACT

The present invention relates to oil-in-water nanoemulsions, processes for their preparation and their use as delivery vehicles for active components for use in opthalmological, dermatological, food, cosmetic, pharmaceutical, agrichemical, textile, polymer and chemical applications. The oil-in-water nanoemulsion comprises up to 40 volume % of an oil phase comprising at least 50 volume % of a triglyceride having a fatty acid chain length of 12 carbon atoms or greater and a hydrophilic non-ionic surfactant having a hydrophilic-lipophilic balance (HLB) greater than 7; and an aqueous phase, in which the oil droplets have an intensity average size of less than 100 nm and the ratio of surfactant to oil is less than 1:1, more preferably 0.2 to 0.8:1.

FIELD

The present invention relates to oil-in-water nanoemulsions, processesfor their preparation and their use as delivery vehicles for activecomponents for use in ophthalmological, dermatological, food, cosmetic,pharmaceutical, agrichemical, textile, polymer and chemicalapplications.

BACKGROUND

Emulsions are colloidal systems which have application in manyindustrial products such as food, cosmetics and pharmaceuticals.Oil-in-water emulsions are made of oil droplets which are dispersed inan aqueous continuous phase. One of the uses of emulsions in industry isto deliver active ingredients and components, such as, flavours,colours, vitamins, antioxidants, anti-microbials, pesticides,herbicides, cosmetics, nutraceuticals, phytochemicals andpharmaceuticals.

The active components can be oil soluble or water soluble, althoughtheir solubility in these environments can vary from highly soluble topoorly soluble. Administering active components that are not soluble inwater poses a challenge as it requires the use of an appropriate vehiclefor bringing an effective amount of the active component into thedesired place of action. Oil-in-water emulsions are commonly used forthe delivery of active components that are not soluble in water. Activecomponents that are soluble in oil are dissolved/dispersed within theoil phase of the emulsion. Active components that are poorly soluble inboth oil and water can be incorporated as part of the interfacial regionof the oil-in-water emulsion.

The emulsions that are conventionally used to deliver active componentssuffer from a number of significant limitations and disadvantages.Emulsions are kinetically stable structures that are subject todestabilisation through a number of mechanisms, ultimately resulting incomplete phase separation of the emulsion. The tendency of emulsions tophysically alter over time presents problems for their storage andhandling. Furthermore this physical degradation increases the likelihoodthat the preparation is in a sub-optimal state when physicallyadministered.

The size (diameter) of a conventional oil-in-water emulsion ranges fromseveral hundred nanometers to several microns. Since these particles arein the order of or greater than the wavelength of light they have anopague appearance. This has the disadvantage of altering the opticalclarity of any product that the emulsion is incorporated into, reducingvisual appeal. Furthermore, emulsions of this size have a lowinterfacial area to volume ratio. This has a negative impact on theemulsions ability to dissolve poorly soluble bioactives which aresoluble at an interface. The amount of a poorly soluble bioactive thatcan be dissolved at an interface being directly linked to the relativeamount of interfacial area.

Another disadvantage of using conventional oil-in-water triglycerideemulsions to deliver active ingredients is that upon oral ingestion therelease of the active ingredient is dependant on the rate and extent oflipolysis. Whilst such emulsions are capable of transporting activeingredients through the aqueous environment of the gastrointestinaltract, the ultimate release of the emulsified active ingredient isdependant on emulsion digestion. The rate of triglyceride emulsiondigestion is a function of many factors, pH, co-lipase/lipaseconcentration, bile salt and emulsion surface area. Principle amongstthem is the relative ratio of emulsion interfacial area to its volume.Emulsions with higher surface area to volume ratios undergo much fasterlipolysis than those with low surface area to volume ratios.

When an emulsion has a particle size of less than 100 nm, the emulsionhas the added benefit of becoming translucent or even transparent. Theformation of very small (sub 100 nm) emulsions has the added benefit ofincreasing the relative amount of interfacial area considerably. Anincrease in the relative amount of interfacial area can lead to agreater ability to dissolve/disperse poorly soluble active components atthe interface. Furthermore, an increase in the relative amount ofinterfacial area can lead to a faster rate of digestion by lipolysiscompared to conventional oil-in-water emulsions. A faster rate oflipolysis can lead to a more rapid release of the emulsified activeingredient.

Two classes of emulsion that can have a particle size less than 100 nmare microemulsions or nanoemulsions. These two classes of emulsion arefundamentally different.

A microemulsion is an emulsion which forms spontaneously as a result ofthe ultralow interfacial tension and the favourable energy of structureformation. Microemulsions are thermodynamically stable having particlesizes that do not change with time. One disadvantage of a microemulsionis that it may become physically unstable if its composition is changed,e.g. upon dilution, acidification or heating. The spontaneous formationof a microemulsion arises from the synergistic interaction ofsurfactant, co-surfactant and co-solvent to effectively “solubilise” oilmolecules. As a result it is known that a disadvantage of microemulsionsis that they contain a high amount of surfactant relative to the amountof oil. In the case of foods, many surfactants have a bitter taste.Furthermore WHO and the FDA have placed restrictions on the dailyintakes of many of these surfactants.

A nanoemulsion is an emulsion which does not form spontaneously, but isinstead formed by the application of shear to a mixture of oil, waterand surfactant. Unlike microemulsions, nanoemulsions are kineticallystable and their particle size may increase over time via coalescence,flocculation and/or Ostwald ripening. The very small size ofnanoemulsions makes them particularly prone to particle size growth byOstwald ripening. An increase in emulsion particle size over time isdisadvantageous as the emulsion will lose its clarity accompanied with acorresponding increase surface area.

Like microemulsions, nanoemulsions can have the benefit of appearingtranslucent/transparent as a result of their small size. Also, likemicroemulsions, nanoemulsions have the benefit of having a highinterfacial area to volume ratio which can aid in the dissolution ofpoorly soluble bioactives and aid the rapid digestion of the emulsion byfaster rates of lipolysis. Furthermore, unlike many microemulsions,nanoemulsions retain their structure (small size) upon dilution and/oracidification. This may have the added benefit of aiding activeadsorption as it is currently thought that emulsions below 100 nm have agreater ability to penetrate epithelial layers such as the skin and oralmucosa. Another advantage of nanoemulsions is that their creationrequires the use of a significantly lower amount of surfactant comparedto microemulsions. This gives the nanoemulsions the advantage that lesssurfactant is incorporated upon addition of a certain amount ofactive/oil. This is beneficial from a toxicological, regulatory andtaste perspective.

The nature of the oil contained within the nanoemulsion is alsoimportant. It is advantageous to have an oil that is a triglyceride asthey present a lower toxicological and/or irrigational profile to humansthan synthetic or hydrocarbon oils. There are three classes oftriglycerides, short chain triglycerides (less than 6 carbons in fattyacid chain), medium chain triglycerides (6 to 12 carbons in fatty acidchain) and long chain triglycerides (greater than 12 carbons in fattyacid chain). It is advantageous if the triglyceride oil within ananoemulsion is of a long chain format, with preferably some degree ofunsaturation as these oils have been shown to provide positivenutritional benefits and are considerably more stable against Ostwaldripening.

The creation of nanoemulsions and/or nanodispersions using medium chaintriglycerides, especially miglyol 812, is known. Medium chaintriglycerides are used as their smaller molecular bulk and highersolubilitiy in water aids their ability to form nanoemulsions and/ornanodispersions. In contrast, it is known that the large molecular bulkof long chain triglycerides prevents them from readily forming clearmicroemulsions or nanoemulsions.

There remains the challenge of creating a nanoemulsion whose oil phasecontains a long chain triglyceride where the emulsion has an intensityaverage size of less than 100 nm, high stability against Ostwaldripening and lower relative amounts of surfactant. The creation of sucha nanoemulsion would be advantageous as it will increase productstability and clarity, improve the solubility of some poorly solubleactives and improve organoleptic properties.

SUMMARY

In a first aspect, there is provided an oil-in-water nanoemulsion whichcomprises

up to 40 volume % of an oil phase comprising at least 50 volume % of atriglyceride having a fatty acid chain length of 12 carbon atoms orgreater;

a hydrophilic non-ionic surfactant having a hydrophilic-lipophilicbalance (HLB) greater than 7; and

an aqueous phase,

in which the oil droplets of the nanoemulsion have an intensity averagesize of less than 100 nm and the ratio of surfactant to oil is less than1:1, more preferably 0.2 to 0.8:1.

In a second aspect, there is provided a process for the preparation ofan oil-in-water nanoemulsion which comprises

subjecting up to 40 volume % of an oil phase comprising at least 50volume % of a triglyceride having a fatty acid chain length of 12 carbonatoms or greater and a hydrophilic non-ionic surfactant having ahydrophilic-lipophilic balance (HLB) greater than 7 and an aqueous phaseto homogenisation, sonication or membrane emulsification to prepare ananoemulsion in which the oil droplets have an intensity average size ofless than 100 nm and the ratio of surfactant to oil is less than 1:1,more preferably 0.2 to 0.8:1.

In a third aspect, there is provided use of the nanoemulsion definedabove as a delivery vehicle for active components.

The active components include ingredients and components for use infood, beverages, cosmetics, pharmaceutical, ophthalmological,dermatological, agrichemical, textile, polymer and chemicalapplications.

There is also provided a delivery vehicle for active componentscomprising the nanoemulsion defined above.

In a fourth aspect, there is provided a formulation comprising thenanoemulsion defined above and an active component.

In a fifth aspect, there is provided a process for the preparation ofthe formulation defined above which comprises mixing the nanoemulsiondefined above with the active component.

In a sixth aspect, there is provided a process for the preparation ofthe formulation defined above which comprises

subjecting the active component, up to 40 volume % of an oil phasecomprising at least 50 volume % of a triglyceride having a fatty acidchain length of 12 carbon atoms or greater and a hydrophilic non-ionicsurfactant having a hydrophilic-lipophilic balance (HLB) greater than 7and an aqueous phase to homogenisation, sonication or membraneemulsification to prepare a nanoemulsion in which the oil particles havean intensity average size of less than 100 nm and the ratio ofsurfactant to oil is less than 1:1, more preferably 0.2 to 0.8:1.

DETAILED DESCRIPTION

The present invention relates to an oil-in-water nanoemulsion, a processof the preparation of the nanoemulsion and the use of the nanoemulsionfor the delivery of active components.

The oil-in-water nanoemulsion comprises

up to 40 volume % of an oil phase comprising at least 50 volume % of atriglyceride having a fatty acid chain length of 12 carbon atoms orgreater and a hydrophilic non-ionic surfactant having ahydrophilic-lipophilic balance (HLB) greater than 7; and

an aqueous phase,

in which the oil droplets have an intensity average size of less than100 nm and the ratio of surfactant to oil is less than 1:1, morepreferably 0.2 to 0.8:1.

In a preferred embodiment, the oil-in-water nanoemulsion comprises up to40 volume % of an oil phase comprising at least 50 volume % of atriglyceride having a fatty acid chain length of 12 carbon atoms orgreater, a hydrophilic non-ionic surfactant having ahydrophilic-lipophilic balance (HLB) greater than 7 and a co-solvent andan aqueous phase.

The nanoemulsion may also contain a co-surfactant which preferablyinteracts synergistically with the non-ionic surfactant to reduceemulsion particle size.

For food, cosmetics, pharmaceuticals, ophthalmological and dermatogicalapplications, it is preferable that components are food grade orpharmaceutical grade thereby resulting in an edible nanoemulsion.

The nanoemulsions have high clarity, are physically stable againstOstwald ripening due to the use of long chain triglycerides and havegood formulation stability as they can be readily diluted to infinitum.The lower surfactant to oil ratio also means that the nanoemulsionsshould have organoleptic appeal as surfactants are generally bitter intaste. The nanoemulsion is preferably food grade or pharmaceutical gradeand the lower surfactant to oil ratio enables the incorporation ofhigher amounts of nanoemulsion into food products before breaching theregulatory level of synthetic surfactants in foods established by WHOand FDA.

Nanoemulsion

The term “nanoemulsion” refers to oil-in-water emulsions in which theoil droplets are ultra small having a diameter of 100 nm or less,preferably 80 nm or less, more preferably 75 nm or less, most preferably60 nm or less. The droplet size is the Z-average or intensity weightedaverage size as measured by dynamic light scattering (also known asphoton correlation spectroscopy).

Oil Phase

The oil phase comprises at least 50 volume % of a triglyceride having afatty acid chain length of 12 carbon atoms or greater. The triglyceridecan be a liquid or solid fat of animal, vegetable, algal or syntheticorigin which is preferably food grade having the following generalformula:

in which R₁, R₂ and R₃ are independently selected from saturated andunsaturated fatty acid residues (unbranched and branched) with chainlengths of C₁₂ or greater, preferably C₁₂-C₂₄, more preferably C₁₆-C₂₂,i.e. long chain triglycerides.

Long chain triglycerides, preferably having some degree of unsaturationhave been shown to provide positive nutritional benefits and areconsiderably more stable against Ostwald ripening. FIG. 1 is a graphdepicting the physical stability of nanoemulsions made using amineral/paraffin oil (hexadecane), a medium chain triglyceride (miglyol812) or a long chain triglyceride (peanut oil). The stability of thelong chain triglyceride is evident from this graph.

Examples of long chain triglycerides include those of animal origin suchas fish oil, cod liver oil, blubber, lard, tallow, schmaltz, and butterfat; vegetable origin such as canola oil, castor oil, cocoa butter,coconut oil, coffee seed oil, corn oil, cotton seed oil, eveningprimrose oil, grapeseed oil, flax seed oil, menhaden oil, mustard seedoil, olive oil, palm oil, palm kernel oil, peanut oil, poppy seed oil,rapeseed oil, rice bran oil, safflower oil, sesame oil, soybean oil,sunflower oil, palm kernel oil, hazelnut oil, sesame oil and wheat germoil; algal origin such as vegetable oil Synthetic triglycerides,fractionated triglycerides, modified triglycerides, hydrogenatedtriglycerides or partially hydrogenated and mixtures of triglyceridesare also included.

The nanoemulsion may contain one or more additional oils such as shortchain triglycerides for example triacetin, tributyrin, tricapylrin andmiglyol; mineral oils for example alkane oils such as decane,tetradecane, hexadecane and octadecane; and flavour oils for examplelimonene, mandarin oil orange oil, lemon oil, lime oil or other citrusoils, peppermint oil, peach oil, vanilla flavour oil and vanillin; andaromatic oils for example peppermint, tea tree oil, eucalyptus oil,mentha arvensis, cedarwood oil, spearmint, orange oil, lemin oil andclove.

The ratio of triglyceride to additional oil is preferably 1:0 to 1:1.

The total amount of oil in the nanoemulsion including long chaintriglyceride and additional oil if present may be 0.01 to 70 wt %,preferably 0.01 to 50 wt %, more preferably 0.01 to 40 wt %.

Hydrophilic Non-Ionic Surfactant

The hydrophilic non-ionic surfactant has a hydrophilic-lipophilicbalance (HLB) greater than 7 and is preferably a food grade orpharmaceutical grade hydrophilic surfactant such as polysorbates(polyethylene glycol sorbitan fatty acid esters), polyethylene glycolalkyl ethers, sugar esters, polyethoxylated fatty acids,polyoxyethylene-polyoxypropylene block co-polymers (Pluronics),polyethylene glycol alkyl phenol surfactants, citric acid esters ofmonoglycerides, polyglycerol esters, polyethoxylated fatty aciddiesters, PEG-fatty acid mono and diesters, polyethylene glycol glycerolfatty acid esters and alcohol oil transesters or mixtures thereof.

Suitable non-ionic surfactants include:

polysorbates for example polyethoxyethylene sorbitan monoesters,including polyoxyethylene sorbitan monolaurate (Tween 20),polyoxyethylene sorbitan monopalmitate (Tween 40), polyoxyethylenesorbitan monostearate (Tween 60), polyoxyethylene sorbitan tristearate(Tween 65) and polyoxyethylene sorbitan mono-oleate (Tween 80);

sugar surfactants for example sucrose monopalmitate, sucrosemonolaurate, sucrose distearate 3 Crodesta F-10, sucrose distearate,monostearate Crodesta F-110, sucrose dipalmitate, sucrose monostearateCrodesta F-160, sucrose monopalmitate, sucrose monolaurate andsaccharose monolaurate;

polyoxyethylene-polyoxypropylene block co-polymers which are availableunder various trade names including Synperonic PE series (ICI),Pluronic® series (BASF), Emkalyx, Lutrol (BASF), Supronic, Monolan,Pluracare and Plurodac.

The polyoxyethylene-polyoxypropylene block co-polymers are also known as“polyoxamers” and have the general formula:

HO(C₂H₄O)_(A)(C₃H₆O)_(B)(C₂H₄O)_(A)H

in which A and B denote the number of polyoxyethylene andpolyoxypropylene units, respectively.

Polyoxamers when A is 1-100 and B is 1-100 and combinations thereof aresuitable for use in the nanoemulsions of the present invention.

The amount of hydrophilic surfactant in the nanoemulsion may be 0.1 to15 wt %, preferably 1 to 10 wt %, more preferably 3 to 7 wt %.

Co-Surfactant

The nanoemulsion may also contain a co-surfactant which is preferably asurfactant that acts synergistically with the hydrophilic non-ionicsurfactant to alter the interfacial curvature. This lowers interfacialtension, permitting easier emulsion formation.

Preferably the co-surfactant is food grade or pharmaceutical grade.

Suitable food grade co-surfactants include:

sorbitan fatty acid esters such as sorbitan monolaurate (Span 20),sorbitan monopalmitate (Span 40), sorbitan tristearate (Span 65),sorbitan monostearate (Span 60), sorbitan monooleate (Span-80) andsorbitan trioleate (Span-85);

phospholipids such as egg/soy lecithin for example epikuron, topcithin,leciprime, lecisoy, emulfluid, emulpur, metarin, emultop, lecigran,lecimulthin, ovothin lyso egg/soy lecithin, hydroxylated lecithinlysophosphatidylcholine, cardiolipin, sphingomyelin,phosphatidylcholine, phosphatidyl ethanolamine, phosphatidic acid,phosphatidyl glycerol, phosphatidyl serine and mixtures of phospholipidswith other surfactants; and

ionic surfactants such as sodium stearoyl lactylate and calcium stearoyllactylate.

The amount of co-surfactant in the nanoemulsion may be 0.1 to 15 wt %.Preferably the co-surfactant is present in a ratio relative to thehydrophilic non-ionic surfactant of 0:1 to 2:1, more preferably 0:1 to1.3:1 and most preferably 0.5:1 to 1.3:1.

Aqueous Phase

The aqueous phase can be either purified or ultrapure water, saline orbuffered saline.

The balance of water after the inclusion of all other formulationcomponents in the nanoemulsion may be 50 to 100 wt %, preferably 40 to99.99 wt %, more preferably 30 to 99.90 wt %.

Co-Solvent

In a preferred embodiment, the nanoemulsion also contains a co-solvent.The co-solvent lowers the interfacial tension of the aqueous phase whichthereby enables the formation of smaller emulsion droplet sizes.

Suitable co-solvents include C₁-C₁₀ alcohols such as methanol, ethanol,propanol, butanol, pentanol, hexanol, heptanol, octanol, nonanol anddecanol; polyols such as glycerol, 1,2 propandiol, 1,3 propandiol,polyethylene glycol and polypropylene glycol; and long chain fattyalcohols. Preferably, the solvent is a C₁-C₄ alcohol, more preferablyethanol.

The amount of solvent in the nanoemulsion may be 0 to 70 wt %,preferably 0 to 50 wt %, more preferably 15 to 45 wt %.

Active Component

The active component is any component that is an oil, oil-soluble,partitions to an oil phase, poorly soluble in oil and water or solubleor capable of being dispersed at an interface which imparts either acolour, aroma, flavour, antimicrobial effect, beautification effect,health promoting effect, disease prevention effect or technique, ordisease curing effect to the nanoemulsion.

The active components may be food or beverage ingredients such as foodsupplements, food additives, aromas, aromatic oils, colours, flavoursand sweeteners; cosmetics; pharmaceuticals such as medicaments,peptides, proteins and carbohydrates; nutraceuticals; phytochemicals;vitamins; essential polyunsaturated fatty acids; plant extracts;agrichemicals such as pestides and herbicides; textiles; polymers; andchemicals.

Suitable active components include:

phytochemicals such as polyphenols (e.g., catechin, epicatechin,epicatechin gallate, quercitin and resveratrol), carotenoids (e.g.,lycopene, lutein, lutein esters, β-carotene, retinyl, retinyl palmitateand zeaxanthin), ubiquinone (CoQ10) and phytosterols;

vitamins such as vitamin A (e.g., retinol and retinol palmitate),Vitamin D (e.g., calciferol), vitamin E (e.g., tocopherol, tocopherolacetate and tocopherol palmitate), vitamin K (e.g., K₁—phylloquinone andK₂—menaquinone)

essential polyunsaturated fatty acids such as linoleic acid,alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid;

flavours such as natural flavour oils for example citrus oil, limonene,mandarin oil orange oil, lemon oil, lime oil, peppermint oil, peach oil,vanilla flavour oil and vanillin or synthetic flavoring materials forexample hexyl alcohol, ethyl laurate, apple flavoring oil, strawberryflavoring oil, benzaldehyde, cinnamic aldehyde, paprica flavoring oil,citronellyl butyrate, phenyl ethyl acetate, ethyl propionate, ethyldecanoate, ethyl butyrate, ethyl hexanoate, brandy flavoring oil, hexylaldehyde, blackberry flavoring oil, phelandrene, blueberry flavoringoil, honey flavoring, oil, nerol, licorice flavoring oil, mapleflavoring oil, ethyl caprylate and watermelon flavoring oil; and

aromatic oils such as peppermint, tea tree oil, eucalyptus oil, menthaarvensis, cedarwood oil, spearmint, orange oil lemin oil and clove.

The amount of active component in the nanoemulsion may be 0.01 to 50preferably 0.01 to 10 wt %.

Additives

The nanoemulsion may contain additives such as stabilisers,antioxidants, preservatives, buffering agents, charge inducing agents,weighting agents polymers and proteins. Stabilisers can be pH modifyingagents, anti-creaming or anti-foaming agents or agents which impartstability to the nanoemulsion. Examples of stabilisers include sodiumoleate, glycerine, xylitol, sorbitol, ascorbic acid, citric acid andsodium edetate. Antioxidants include carotenoids, for examplealpha-tocopherol or its derivatives, which are members of the Vitamin Efamily, β-carotene, lutein, lycopene, ascorbic acid, trolox, β-carotene,polyphenols such as catechin, epicatechin, epicatechin gallate,quercetin, resveratrol, ascorbyl palmitate and butylated hydroxytoluene(BHT). Buffering agents include sodium phosphate, citric acid, formicacid and ascorbic acid. Examples of charge inducing agents includesodium deoxycholate, sodium lauryl sulfate, deoxycholic acid,stearylamine, oleylamine, chitosan and cetyltriethylammonium bromide.Weighting agents include brominated vegetable oils. Examples of polymersand proteins include hydrocolloids such as guar gum, pectin, xanthan andalginate.

The amount of additive in the nanoemulsion may be 0 to 50 wt %,preferably 0 to 25 wt %, more preferably 0 to 10 wt %.

Process

The process for preparing nanoemulsion in its broadest sense includessubjecting the oil phase comprising the triglyceride, hydrophilicsurfactant, aqueous phase and the co-solvent and/or co-surfactant whenpresent to homogenisation, sonication or membrane emulsification,preferably high shear homogenisation. The interaction between thehydrophilic surfactant and the co-solvent and/or the co-surfactant whenpresent reduces the interfacial tension of the emulsion which leads tobetter homogenisation and a smaller nanoemulsion particle size. Thehomogenisation can be performed using any suitable known homogenisationapparatus such as a microfluidiser (such as Microfluidics M-110YMicrofluidiser made by MFIC Corporation), high pressure homogeniser(such as one made by Gauline, Avestin or Niro Soavi the like) or a probesonicator at pressures such as 1000 bar. Examples of apparatus which canbe used for sonication include Hielscher ultrasonic homogenisers,Branson ultrasonic homogenisers, Cole-Palmer ultrasonic homogenisers orOmni Ruptor 4000 ultrasonic homogenisers. The membrane emulsificationcan be performed using for example a Polytron PT 3100 membranehomogeniser or a LiposoFast membrane homogeniser (Avestin, Canada). Thenumber of passes through the homogenisation apparatus can vary dependingon the desired particle size of the nanoemulsions, usually 5 passes willsuffice.

In one embodiment, the nanoemulsion can be prepared by adding thehydrophilic surfactant and the co-surfactant to the oil phase comprisingtriglyceride and additional oil if present. Preferably the triglycerideoil and the additional oil are premixed. The oil/surfactant combinationis then mixed with a solution containing the aqueous phase and theco-solvent using any suitable known mixing apparatus such as a Silversonrotor stator mixer at 12,000 rpm for about 2 minutes to form apre-emulsion. The pre-emulsion is then subjected to homogenisation.

The formulation can be prepared by mixing the nanoemulsion with theactive component, preferably by stirring at room temperature for asuitable period of time such as 12 hours at room temperature or severalhours at elevated temperatures for example 60° C. In another embodiment,the formulation can be prepared by mixing the active component with thecomponents of the emulsion and the resulting mixture is thenhomogenised. The final formulation is generally clear which indicatesthat the nanoemulsion has dissolved/incorporated the active component.

Formulation

The nanoemulsion can function as a delivery vehicle for activecomponents which may be soluble in oil, partition to an oil phase or arepoorly soluble in both oil and water. The active components can beentrapped in the nanoemulsion and incorporated into a formulationmaintaining its stability.

It will be appreciated by those skilled in the art that is it mostpreferable to prepare the nanoemulsion as a concentrate, preferably withan oil content of 15 to 40 volt. The same nanoemulsions can also beprepared at much lower oil contents, e.g. 0.1 to 10 volt. Whilst it ispreferable for the nanoemulsion to be prepared as a concentrate, it isalso preferable to add the nanoemulsion to a food product in a dilutedform ranging from 0.01 to 30 volt.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph comparing the change in nanoemulsion particle sizeover time for two triglyceride nanoemulsions made using i) a mediumchain triglyceride (miglyol 812) and ii) a long chain triglyceride(peanut oil).

FIG. 2 are graphs describing the typical particle size distributions ofnanoemulsions described in examples 2-6 as i) a intensity weightedparticle size distribution ii) a volume weighted particle sizedistribution as measured by dynamic light scattering.

FIG. 3 is a graph showing the typical physical stability (change inaverage particle size over time during storage at 24° C.) ofnanoemulsions outlined in examples 2-6.

FIG. 4 is a graph comparing the ability of different sized canola oilemulsions to solubilise (dissolve) phytosterol. The emulsions were i) aconventional canola oil emulsion (600 nm diameter, 0.5 wt % polysorbate80) ii) a high shear homogenised canola oil emulsion (160 nm diameter,5.6 wt % polysorbate 80), iii) a microfluidized canola oil emulsion (130nm diameter, 5.6 wt % polysorbate 80) iv) a canola oil nanoemulsion asoutlined in Example 5 (50 nm diameter).

FIG. 5 is a graph comparing the solubility of resveratrol in i) water,ii) a long chain triglyceride, iii) a conventional long chaintriglyceride emulsion (0.6 μm diameter, 0.5 wt % polysorbate 80) and iv)a edible nanoemulsion as outlined in example 11.

EXAMPLES

The invention will now be described with reference to the followingnon-limiting examples.

Processing Conditions

A triglyceride oil nanoemulsion was prepared by creating a pre-emulsionof a mixture of ingredients as outlined in the below examples using asilverson rotor stator mixer at 12,000 rpm for 2 minutes. Nanoemulsionswere prepared from pre-emulsions using a Microfluidics M-110Ymicrofluidizer (MFIC Corporation, Newton, Mass., USA) with a F20 Y 75 μminteraction chamber and H30 Z 200 μm auxiliary chamber inline.Transparent nanoemulsions were prepared by subjecting pre-emulsions to 5passes (unless otherwise stated) at 1000 bar.

Formulation Examples

The examples of formulations set out below have several factors thatcontribute to the small emulsion size. It is an interaction between theoil (or a mixture of oils), a hydrophilic surfactant, a co-solvent and aco-surfactant that creates a favourably low interfacial tension thatenables the reduction of the emulsion particle size to around 50-60 nm.The main formulation is a triglyceride oil with a side chain lengthequal to or greater than 12 carbons, polyoxyethylene sorbitan mono ester(Tween) as the hydrophilic surfactant and ethanol as the co-solvent.Different types of nanoemulsion arise from the different co-surfactantsused these include: various lecithins, sorbitan monoester surfactants(Span) and sodium stearoyl lactylate and many like co-surfactants.

All of the formulation examples have been found to work equally wellwith any of the triglyceride oils.

Example 1: A Peanut Oil Nanoemulsion—Tween/Ethanol

A peanut oil in water nanoemulsion was prepared by adding 12 grams ofpolyoxyethylene sorbitan mono-oleate (Tween 80) to 23 grams of peanutoil. This oil/surfactant mixture was then intermixed into 120 g of a 3to 2 water to ethanol solution with a Silverson rotor stator mixer at12,000 rpm for 2 minutes to form a pre-emulsion. The pre-emulsion wasthen homogenised with a Microfluidizer™ at 1000 bar and 5 passes. Theresulting nanoemulsion had a particle size of 45 nm, and high opticalclarity. If diluted with water (10 to 99% dilution) the nanoemulsionexhibited no change in size over a 100 day storage period.

Oil Content:

If the ratio of Tween 80 to oil are kept the same this formulation willwork up to an oil content of 25-30%.

This formulation will work equally well with the followingsubstitutions:

Polyoxyethylene Surfactant:

Tween 40 and Tween 60. Tween contents ranging from 6 g to greater than30 g.

Ethanol Content:

an aqueous phase ethanol content ranging from 20 to 50%.

Fat/Oil:

Lard, butter fat, canola oil, rapeseed oil, fish oil, sunflower oil,flax seed oil, safflower oil, palm oil, coconut oil, soybean oil, oliveoil, corn oil, or any other tri-glyceride oil or combinations thereof.

Example 2: A Flax Seed Oil Nanoemulsion—Tween/Ethanol/Emultop IP

A flax seed oil nanoemulsion was prepared by adding 8 grams ofpolyoxyethylene sorbitan mono-oleate (Tween 80) and 5 grams of EmultopIP (lysolecithin) to 22.5 grams of flax seed oil. This oil/surfactantmixture was then intermixed into 120 g of a 3 to 1 water to ethanolsolution with a silverson rotor stator mixer at 12,000 rpm for 2 minutesto form a pre-emulsion. The pre-emulsion was then homogenised with amicrofluidiser at 1000 bar and 5 passes. The resulting nanoemulsion hada particle size of 45 nm, had high optical clarity and did not changesize or optical clarity over a 100 day storage period.

Oil Content:

If the ratio of between 80 and co-surfactant to oil are kept the samethis formulation will work up to an oil content of 25-30%.

This formulation will work equally well with the followingsubstitutions:

Polyoxyethylene Surfactant:

Tween 40 and Tween 60. Tween contents ranging from 6 g up to 30 g.

Ethanol Content:

an aqueous phase ethanol content ranging from 20 to 50%.

Fat/Oil:

Lard, butter fat, canola oil, rapeseed oil, fish oil, sunflower oil,peanut oil, safflower oil, palm oil, coconut oil, soybean oil, oliveoil, corn oil, or any other tri-glyceride oil or combinations thereof.

Example 3: A Tuna Oil Nanoemulsion—Tween/Ethanol/Centromix E

A tuna oil nanoemulsion was prepared by adding 8 grams ofpolyoxyethylene sorbitan mono-oleate (Tween 80) and 8 grams of CentromixE (lysolecithin) to 22.5 grams of tuna oil. This oil/surfactant mixturewas then intermixed into 120 g of a 3 to 1 water to ethanol solutionwith a silverson rotor stator mixer at 12,000 rpm for 2 minutes to forma pre-emulsion. The pre-emulsion was then homogenised with amicrofluidiser at 1000 bar and 5 passes. The resulting nanoemulsion hada particle size of 45 nm, had high optical clarity and did not changesize or optical clarity over a 100 day storage period.

Oil Content:

If the ratio of Tween 80 and co-surfactant to oil are kept the same thisformulation will work up to an oil content of 25-30%.

This formulation will work equally well with the followingsubstitutions:

Polyoxyethylene Surfactant:

Tween 40 and Tween 60. Tween contents ranging from 6 g up to 30 g.

Ethanol Content:

an aqueous phase ethanol content ranging from 20 to 50%.

Oil:

Canola oil, rapeseed oil, fish oil, sunflower oil, peanut oil and flaxseed oil.

Example 4: A Peanut Oil Nanoemulsion—Tween/Ethanol/Span 80

A peanut oil nanoemulsion was prepared by adding 8 grams ofpolyoxyethylene sorbitan mono-oleate (Tween 80) and 6 grams of sorbitanmono-oleate (Span 80) to 22.5 grams of peanut oil. This oil/surfactantmixture was then intermixed into 120 g of a 3 to 1 water to ethanolsolution with a silverson rotor stator mixer at 12,000 rpm for 2 minutesto form a pre-emulsion. The pre-emulsion was then homogenised with amicrofluidiser at 1000 bar and 5 passes. The resulting nanoemulsion hada particle size of 45 nm, had high optical clarity and did not changesize or optical clarity over a 100 day storage period.

Oil Content:

If the ratio of between 80 and co-surfactant to oil are kept the samethis formulation will work up to an oil content of 25-30 Thisformulation will work equally well with the following substitutions:

Polyoxyethylene Surfactant:

Tween 40 and Tween 60. Tween contents ranging from 6 g up to 30 g.

Ethanol Content:

an aqueous phase ethanol content ranging from 20 to 50%.

Oil:

Canola oil, rapeseed oil, fish oil, sunflower oil and flax seed oil

Example 5: A Canola Oil Nanoemulsion—Tween/Ethanol/Sodium SteroylLactylate

A canola oil nanoemulsion was prepared by adding 8 grams ofpolyoxyethylene sorbitan mono-oleate (Tween 80) and 5 grams of sodiumstearoyl lactylate (SSL) to 22.5 grams of canola oil. Thisoil/surfactant mixture was then intermixed into 120 g of a 3 to 1 waterto ethanol solution with a silverson rotor stator mixer at 12,000 rpmfor 2 minutes to form a pre-emulsion. The pre-emulsion was thenhomogenised with a microfluidiser at 1000 bar and 5 passes. Theresulting nanoemulsion had a particle size of 45 nm, had high opticalclarity and did not change size or optical clarity over a 100 daystorage period.

Oil Content:

If the ratio of between 80 and co-surfactant to oil are kept the samethis formulation will work up to an oil content of 25-30%.

This formulation will work equally well with the followingsubstitutions:

Polyoxyethylene Surfactant:

Tween 40, Tween 60 and Tween 80, Tween contents ranging from 6 g up to30 g.

Ethanol Content:

an aqueous phase ethanol content ranging from 20 to 50%.

Oil:

Rapeseed oil, fish oil, sunflower oil, peanut oil and flax seed oil.

Example 6: A Mixed Oil Nanoemulsion—Tween/Ethanol/Lecithin

A mixed triglyceride oil nanoemulsion was prepared by adding 8 grams ofpolyoxyethylene sorbitan mono-oleate (Tween 80) and 8 grams of CentromixE (lysolecithin) to 22 g of a 50:50 mixture of peanut oil and miglyolthat had been thoroughly premixed. This oil/surfactant mixture was thenintermixed into 120 g of a 3 to 1 water to ethanol solution with asilverson rotor stator mixer at 12,000 rpm for 2 minutes to form apre-emulsion. The pre-emulsion was then homogenised with amicrofluidiser at 1000 bar and 5 passes. The resulting nanoemulsion hada particle size of 45 nm, had high optical clarity and did not changesize or optical clarity over a 100 day storage period.

This formulation will work equally well with the followingsubstitutions:

Polyoxyethylene Surfactant:

Tween 40, Tween 60 and Tween 80.

Oil:

Canola oil, rapeseed oil, fish oil, sunflower oil and flax seed oil.

Ethanol Content:

an aqueous phase ethanol content ranging from 20 to 50%.

Substitutions:

The additional oil, miglyol can be substituted with any mutuallymiscible oil including: tributyrn, tricapylrin, triacetin, limonene,orange oil, lemon oil, decane, tetradecane and hexadecane.

Example 7: Flavour Oil Nanoemulsion Example a Clear Orange Oil FlavourConcentrate

An orange flavour oil nanoemulsion was prepared by first thoroughlymixing 9 g of orange oil with 11.5 grams of peanut oil. To this mixtureof orange oil/peanut oil 8 grams of polyoxyethylene sorbitan mono-oleate(Tween 80) and 5 grams of Emultop IP (lysolecithin) were added. Thisoil/emulsifier mixture was then intermixed into 120 g of a 3 to 1 waterto ethanol solution with a silverson rotor stator mixer at 12,000 rpmfor 2 minutes to form a pre-emulsion. The pre-emulsion was thenhomogenised with a microfluidiser at 1000 bar and 5 passes. Theresulting orange flavour nanoemulsion had a particle size of 45 nm andhad high optical clarity. This orange flavour oil nanoemulsion was addedto sparkling water at 0.01 wt % to create an orange flavoured sparkingwater.

Comparative Examples

TABLE 1 Summary of size, clarity and physical stability of dispersionsmade formulations using a medium chain triglyceride miglyol Dilutablewith water (clarity maintained High Sta- with Example Oil core Sizeclarity ble dilution) 8 - nano- Miglyol 812 <40 nm  yes No no dispersion9 - Miglyol 812 45 nm yes No yes nanoemulsion 10 - Miglyol 812 60 nm yesNo yes nanoemulsion Comparative Example 8: Medium chain triglycerideoil-in- water nanodispersions Soybean lecithin 17.3% Polysorbate 8034.0% Miglyol 812 34.5% ethanol 14.2%

Preparation: Part A—Nanodispersion:

Miglyol 812 and polysorbate 80 were mixed. The soybean lecithin wasdissolved in ethanol and added to this mixture with stirring from amagnetic stirring mantle. The resulting solution was a clear homogeneousliquid, indicating the formation of nanodispersion.

Part B—Dilution with Water:

Dilution of this solution with water at 50° C., to an oil content of10%, lead to the formation of a turbid white dispersion that had anaverage particle size of 2 micrometers, indicating the formation of aconventionally sized emulsion.

Comparative Example 9: Medium Chain Triglyceride Nanoemulsion

A medium chain triglyceride nanoemulsion was prepared by adding 8 gramsof polyoxyethylene sorbitan mono-ester (Tween 80) and 8 grams ofCentromix E (lysolecithin) to 22 g of miglyol 812 that had beenthoroughly premixed. This oil/surfactant mixture was then intermixedinto 120 g of a 3 to 1 water to ethanol solution with a silverson rotorstator mixer at 12,000 rpm for 2 minutes to form a pre-emulsion. Thepre-emulsion was then homogenised with a Microfluidizer™ at 1000 bar and5 passes. The resulting nanoemulsion had an initial particle size of 45nm and initially had high optical clarity. However, this nanoemulsionwas unstable to Ostwald ripening and its size increased over severalweeks to the point where the nanoemulsion lost clarity, refer to FIG. 1.

Comparative Example 10: Medium Chain Triglyceride Nanoemulsion UsingTween 80

A medium chain triglyceride nanoemulsion was prepared by adding 24 gramsof polyoxyethylene sorbitan mono-ester (Tween 80) to 23.5 g of miglyol812. This oil/surfactant mixture was then intermixed into 120 g of waterwith a silverson rotor stator mixer at 12,000 rpm for 2 minutes to forma pre-emulsion. The pre-emulsion was then homogenised with aMicrofluidizer™ at 1000 bar and 5 passes. The resulting dispersion had atransparent bluish colour and a particle size of 60 nm indicating theformation of a high clarity nanoemulsion of a medium chain triglyceride.However, this nanoemulsion was unstable to Ostwald ripening and its sizeincreased over several weeks to the point where the nanoemulsion lostclarity over four weeks.

Bioactive Delivery Examples Example 11: Resveratrol Nanoemulsion

A nutritional supplement was created by intermixing powdered resveratrolwith a clear triglyceride nanoemulsion. Briefly, 300 mg of high purityresveratrol was intermixed with 100 ml of a nanoemulsion formulatedaccording to any of examples 1-3 by stirring at room temperature for 4hours. The resulting solution was clear and there way no indication ofinsoluble resveratrol particles, indicating that the nanoemulsion haddissolved the resveratrol.

This formulation will work equally well with the followingsubstitutions:

The resveratrol is added to the emulsion ingredient mixture, as a solidpowder or dissolved/dispersed in one of the ingredients, either prior topre-emulsion formation or just prior to microfluidization.

Example 12: Phytosterol Nanoemulsion

A nutritional supplement was created by dispersing powdered phytosterolwith the oil phase ingredients (triglyceride oil, surfactant and/orco-surfactant) of examples 1-7 and heating above 100° C. This solutionof phytosterol, oil and surfactant was then intermixed with 120 g of a 3to 1 water to ethanol solution using a silverson rotor stator mixer at12,000 rpm for 2 minutes to form a pre-emulsion. The pre-emulsion wasthen homogenised with a Microfluidizer™ at 1000 bar and 5 passes. Theresulting nanoemulsion had an initial particle size of 45 nm and highoptical clarity. HPLC analysis demonstrated that nanoemulsions preparedin this way were capable of dissolving to a much greater extent comparedto oil, or a conventionally sized emulsion FIG. 3.

Example 13: β-Carotene Nanoemulsion

A nutritional supplement, or natural coloring agent was created bynanoemulsifying fi-carotene that was dissolved/dispersed in atriglyceride oil. 23 g of a β-carotene loaded oil (e.g. Betatene 30% inolive oil) was thoroughly mixed with 8 grams of polyoxyethylene sorbitanmono-oleate (Tween 80) and 8 grams of Centromix E (lysolecithin). Thisoil/surfactant mixture was then intermixed into 120 g of a 3 to 1 waterto ethanol solution with a silverson rotor stator mixer at 12,000 rpmfor 2 minutes to form a pre-emulsion. The pre-emulsion was thenhomogenised with a Microfluidizer™ at 1000 bar and 5 passes. Theresulting nanoemulsion had a particle size of 50 nm, had high opticalclarity, a natural deep red colour, and did not change size over a 30day storage period.

Example 14: Lutein Nanoemulsion

A nutritional supplement, or natural coloring agent was created bynanoemulsifying a mixture of lutein and lutein esters that weredissolved/dispersed in a triglyceride oil. 23 g of a lutein/lutein esterloaded oil (e.g. Xangold 15% in olive oil from Cognis) was thoroughlymixed with 8 grams of polyoxyethylene sorbitan mono-oleate (Tween 80)and 8 grams of Centromix E (lysolecithin). This oil/surfactant mixturewas then intermixed into 120 g of a 3 to 1 water to ethanol solutionwith a silverson rotor stator mixer at 12,000 rpm for 2 minutes to forma pre-emulsion. The pre-emulsion was then homogenised with aMicrofluidizer™ at 1000 bar and 5 passes. The resulting nanoemulsion hada particle size of 50 nm, had high optical clarity, a natural deeporange colour, and did not change size over a 30 day storage period.

Example 15: Retinyl Palmitate Nanoemulsion

A nutritional supplement, a natural colouring agent, or a cosmeticingredient was created by nanoemulsifying a 1:1 mixture of; retinylpalmitate in oil and vegetable oil. Briefly, 12 g of a retinyl palmitateloaded sunflower oil (e.g. Vitamin A-Palmitate 1.0 Mio IU/G—BASF) and 12g of sunflower oil, were thoroughly mixed with 8 grams ofpolyoxyethylene sorbitan mono-oleate (Tween 80) and 8 grams of CentromixE (lysolecithin). This oil/surfactant mixture was then intermixed into120 g of a 3 to 1 water to ethanol solution with a silverson rotorstator mixer at 12,000 rpm for 2 minutes to form a pre-emulsion. Thepre-emulsion was then homogenised with a Microfluidizer™ at 1000 bar and5 passes. The resulting nanoemulsion had a particle size of 50 nm, hadhigh optical clarity, a natural yellow colour, and did not change sizeover a 100 day storage period.

The above tuna oil examples can also act as a bioactive example as tunaoil is a bioactive.

In the subject specification except where the context requires otherwisedue to express language or necessary implication, the word “comprise” orvariations such as “comprises” or “comprising” is used in an inclusivesense, i.e. to specify the presence of the stated features but not topreclude the presence or addition of further features in variousembodiments of the invention.

It will be understood to persons skilled in the art of the inventionthat many modifications may be made without departing from the spiritand scope of the invention.

1. An oil-in-water nanoemulsion which comprises up to 40 volume % of anoil phase comprising at least 50 volume % of a triglyceride having afatty acid chain length of 12 carbon atoms or greater; a hydrophilicnon-ionic surfactant having a hydrophilic-lipophilic balance (HLB)greater than 7; and an aqueous phase, in which the oil droplets of thenanoemulsion have an intensity average size of less than 100 nm and theratio of surfactant to oil is less than 1:1.
 2. A nanoemulsion accordingto claim 1 in which the oil droplets have a diameter of 80 nm or less,75 nm or less or 60 nm or less.
 3. A nanoemulsion according to claim 1in which the triglyceride is fish oil, cod liver oil, blubber, lard,tallow, schmaltz, and butter fat; vegetable origin such as canola oil,castor oil, cocoa butter, coconut oil, coffee seed oil, corn oil, cottonseed oil, evening primrose oil, grapeseed oil, flax seed oil, menhadenoil, mustard seed oil, olive oil, palm oil, palm kernel oil, peanut oil,poppy seed oil, rapeseed oil, rice bran oil, safflower oil, sesame oil,soybean oil, sunflower oil, palm kernel oil, hazelnut oil, sesame oil,wheat germ oil, vegetable oil, synthetic triglyceride, fractionatedtriglyceride, modified triglyceride, hydrogenated triglyceride,partially hydrogenated triglyceride or mixtures thereof.
 4. Ananoemulsion according to claim 3 which further comprises one or moreadditional oils.
 5. A nanoemulsion according to claim 4 in which theratio of triglyceride to additional oil is 1:0 to 1:1.
 6. A nanoemulsionaccording to claim 5 in which the total amount of oil in thenanoemulsion comprising triglyceride and additional oil if present is0.01 to 70 wt %, 0.01 to 50 wt % or 0.01 to 40 wt %.
 7. A nanoemulsionaccording to claim 1 in which the hydrophilic non-ionic surfactant isselected from polysorbates, polyethylene glycol alkyl ethers, sugaresters, polyethoxylated fatty acids, polyoxyethylene-polyoxypropyleneblock co-polymers, polyethylene glycol alkyl phenol surfactants, citricacid esters of monoglycerides, polyglycerol esters, polyethoxylatedfatty acid diesters, PEG-fatty acid mono and diesters, polyethyleneglycol glycerol fatty acid esters and alcohol oil transesters ormixtures thereof.
 8. A nanoemulsion according to claim 1 in which theamount of hydrophilic surfactant is 0.1 to 15 wt %, 1 to 10 wt % or 3 to7 wt %.
 9. A nanoemulsion according to claim 1 which further comprises aco-solvent.
 10. A nanoemulsion according to claim 9 in which the amountof co-solvent is 0 to 70 wt %, 0 to 50 or 15 to 45 wt %.
 11. Ananoemulsion according to claim 1 which further comprises aco-surfactant.
 12. A nanoemulsion according to claim 11 in which theamount of co-surfactant is 0.1 to 15 wt %.
 13. A nanoemulsion accordingto claim 11 in which the co-surfactant is present in a ratio relative tothe hydrophilic non-ionic surfactant of 0:1 to 2:1, 0:1 to 1.3:1 or0.5:1 to 1.3:1.
 14. A nanoemulsion according to claim 1 in which balanceof water is 50 to 100 wt %, 40 to 99.99 wt % or 30 to 99.90 wt %.
 15. Aprocess for the preparation of an oil-in-water nanoemulsion according toclaim 1 which comprises subjecting up to 40 volume % of an oil phasecomprising at least 50 volume % of a triglyceride having a fatty acidchain length of 12 carbon atoms or greater and a hydrophilic non-ionicsurfactant having a hydrophilic-lipophilic balance (HLB) greater than 7and an aqueous phase to homogenisation, sonication or membraneemulsification to prepare a nanoemulsion in which the oil droplets havean intensity average size of less than 100 nm and the ratio ofsurfactant to oil is less than 1:1.
 16. A delivery vehicle for an activecomponent comprising the nanoemulsion according to claim
 1. 17. Aformulation comprising the nanoemulsion according to claim 1 and anactive component.
 18. A formulation according to claim 17 in which theactive component is selected from food supplements, food additives,aromas, aromatic oils, colours, flavours, sweeteners, cosmetics,pharmaceuticals, nutraceuticals, phytochemicals, vitamins, essentialpolyunsaturated fatty acids, plant extracts, agrichemicals, textiles,polymers and chemicals.
 19. A process for the preparation of theformulation according to claim 17 which comprises mixing thenanoemulsion with the active component.
 20. A process for thepreparation of the formulation according to claim 17 which comprisessubjecting the active component, up to 40 volume % of an oil phasecomprising at least 50 volume % of a triglyceride having a fatty acidchain length of 12 carbon atoms or greater and a hydrophilic non-ionicsurfactant having a hydrophilic-lipophilic balance (HLB) greater than 7and an aqueous phase to homogenisation, sonication or membraneemulsification to prepare a nanoemulsion in which the oil particles havean intensity average size of less than 100 nm and the ratio ofsurfactant to oil is less than 1:1.